4-Aminophenol → 4-(4-Aminophenoxy)-N-methylpicolinamide

Temperatur

80 °C

A solution of 4-aminophenol (9.60 g, 88.0 mmol) in anh. DMF (150 mL) was treated with potassium tert-butoxide (10.29 g, 91.7 mmol), and the reddish-brown mixture was stirred at room temp. for 2 h. The contents were treated with 4-chloro-N-methyl-2-pyridinecarboxamide (15.0 g, 87.9 mmol) and K2CO3 (6.50 g, 47.0 mmol) and then heated at 80° C. for 8 h. The mixture was cooled to room temp. and separated between EtOAc (500 mL) and a saturated NaCl solution (500 mL). The aqueous phase was back-extracted with EtOAc (300 mL). The combined organic layers were washed with a saturated NaCl solution (4×1000 mL), dried (Na2SO4) and concentrated under reduced pressure. The resulting solids were dried under reduced pressure at 35° C. for 3 h to afford 4-(2-(N-methylcarbamoyl)-4-pyridyloxy)aniline as a light-brown solid 17.9 g, 84%): 1H-NMR (DMSO-d6) δ 2.77 (d, J=4.8 Hz, 3H), 5.17 (br s, 2H), 6.64, 6.86 (AA′BB′ quartet, J=8.4 Hz, 4H), 7.06 (dd, J=5.5, 2.5 Hz, 1H), 7.33 (d, J=2.5 Hz, 1H), 8.44 (d, J=5.5 Hz, 1H), 8.73 (br d, 1H); HPLC ES-MS m/z 244 ((M+H)+).

1. temperatureThe mixture was cooled to room temp.
2. customseparated between EtOAc (500 mL)
3. extractionThe aqueous phase was back-extracted with EtOAc (300 mL)
4. washThe combined organic layers were washed with a saturated NaCl solution (4×1000 mL)
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated under reduced pressure
7. customThe resulting solids were dried under reduced pressure at 35° C. for 3 h

ORD-Eintrag

ord-5dab120957ca46cc88223073c36d82a1

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08841330B2